Mini Review: Risk Assessment, Clinical Manifestation, Prediction, and Prognosis of Mucormycosis: Implications for Pathogen- and Human-Derived Biomarkers

Abstract

Mucormycosis is a fungal disease caused by members of the fungal order Mucorales, which are abundantly found in terrestrial environments. The fungi propagate clonally via mitospores, which are transmitted to humans through the air and cause superficial or invasive infections. The disease has emerged in recent years and coincides generally with immunosuppression on the patient side. Mucormycosis is still rarely recognized in the clinical because of its unspecific symptoms which often triggers misdiagnosis with bacterial or viral infections leading to prolonged therapeutic cycles and loss of valuable time to manage mucormycosis properly. Infected patients develop various clinical forms, most notably ranging from rhinocerebral via pulmonary to gastrointestinal forms. Traditional diagnosis is based on culture and histopathologic examinations of the affected tissue. But, the achievement of a precise result is time-consuming, labor-intensive, requires mycological expertise and the finding appears often too late. A rapid and precise diagnosis is mandatory because symptoms are non-specific and the disease is rapidly progressing with often fatal outcome. Mucormycosis was increasingly associated with other infections and underlying conditions and risk factors causing comorbidities, which are difficult to successfully manage. This mini-review summarizes the current knowledge on the epidemiology and causative agents of mucormycosis, transmission, risk factors, clinical presentation, diagnosis, and highlights the lack of appropriate biomarkers on the pathogen and the host sides for rapid pathogen and host susceptibility detection, respectively. Fungal antigens and single nucleotide polymorphisms (SNPs) in human host genes are useful for the assessment of susceptibility. This mini-review addresses possibilities for early prediction of susceptibility to mucormycosis based on forecasting of the risk of infection with fungal pathogens other than Mucorales. The topic of early prediction and diagnosis of mucormycosis represents a current research gap and highlights the importance of potential future developments in the area of risk assessment, susceptibility prognosis in conjunction with early diagnosis to reduce mortality in patients suffering from mucormycosis.

Mucormycosis threats: A systemic review

“…For serological diagnosis, the levels of dihexasaccharide in the serum could also be assessed using Matrix‐associated Laser Desorption Ionization‐Time of Flight (MALDI‐TOF). A significant relevance of the serum levels of dihexasaccharide and incidence of mucormycosis have been reported [40]. Earlier in this article, we have discussed about the significance of CotH surface coat protein in the prevalence of the infection.…”

“…Early diagnosis could be achieved by detecting for circulating pathogenic DNA in the serum by performing the qPCR analysis [40].…”

“…The available diagnostic kits; ID32C and API 50 CH specifically used to identify Zygomycetes, not for M. circinelloides and M. rouxii [38]. Additionally, optical brighteners termed as blankophor and calcofluor could be used for examining specimens such as sputum, bronchoscopic specimens, or lung tissue which may appear as nonseptate or broad pauci-septate, coenocytic to irregular large branching, length (6-25 μm), irregular hyphae [39][40][41]. Off note, histopathologic examinations did not consider as a standalone method for identification, as Aspergillus and other species show morphological similarities [37].…”

“…ITS is the most widely sequenced genomic region for fungi or it is often referred to as the unique fungal barcode sequence [30]. Early diagnosis could be achieved by detecting for circulating pathogenic DNA in the serum by performing the qPCR analysis [40].…”

An old confusion: Entomophthoromycosis versus mucormycosis and their main differences

“…However, much of the scientific literature, especially case reports, retained or confused the definitions. The pathogens of the order Mucorales (subphylum: Mucoromycotina ) are associated with mucormycosis and belong to the genera Rhizopus , Mucor , Lichtheimia , Cunninghamella , Apophysomyces , Rhizomucor , Saksenaea , Synchephalastrum , Thamnostylum , Cokeromyces , Actinomucor , Cokeromyces ( Acosta-España and Voigt, 2022 ). Entomophthoromycosis is caused by species of orders Basidiobolales and Entomophthorales which are Basidiobolus and Conidiobolus , respectively (both in the subphylum: Entomophthoromycotina).…”